The adenoviruses cause enteric or respiratory infection in humans as well as in domestic and laboratory animals. The adenovirus fibre protein plays an essential role in viral attachment by interacting with specific cellular receptors which facilitate entry into susceptible host cells. Thus the fibre protein determines the specific tissue tropism of a particular adenovirus (Chroboczek et al., 1995). The fibre is therefore considered the most important viral surface molecule in virion attachment to target cells.
In order to exploit this targeting property, several methods have been used to change the fibre protein carried by particular human adenoviruses. Several approaches have been undertaken to retarget adenovirus particles to different cell types, including the use of recombinant adenoviruses with modified fibre structure (Wickham et al., 1997; Dimitriev et al., 1998; Wirtz et al., 1999), single-chain antibodies (scFv) (Watkins et al., 1997; Douglas et al., 1999), chimeric fibre proteins (Krasnykh et al., 1996; Stevenson et al., 1997) and exchange of fibre proteins of different serotypes (Gall et al., 1996). These approaches either require the genetic manipulation of the adenovirus genome which reduces the already limited available space for incorporation of foreign genes into the viral genome, or complexing of bi-specific conjugates with adenovirus particles.
Using a different approach, Von Seggern, et al. (1998) constructed a cell line which stably expressed the Human Adenovirus serotype 5 (HAdV5) fibre protein. After passaging HAdV3 through this cell line, virus particles contained the serotype 5 fibre protein. Growth of a fibre defective mutant HAdV in this cell line allowed the generation of fibre positive Human adenovirus.
Additionally, cell lines expressing genes which enable complementation of adenoviral vectors with deletions in a number of regulatory genes have also been reported (Wang et al., 1995; Amalfitano et al., 1996; Amalfitano et al., 1997).
All the work thus far published on fibre-directed targeting appears to be focussed on re-directing the adenovirus from one specific target tissue type to another specific target tissue, and in some cases greatly restricting the target cells to which the adenovirus can attach. Additional methods are still needed to broaden the target tissue types in the animal to which the recombinant adenovirus can bind. Such methods may be useful in increasing or up-regulating either the amount and/or quality of the immune response generated against a particular antigen or the therapeutic effect of an immunomodulatory molecule.